At present, lung cancer is one of the malignant tumors with the fastest growth of morbidity and mortality, as well as the largest threat to population health and life.
However, although there are many kinds of drugs for the treatment of lung cancer on the market, all of them have various defects, such as low bioavailability, bad specificity, great toxic and side effect and so on. While these shortcomings are often due to the structural features of compounds themselves and their targets, that are difficult to overcome in the further study.
Therefore, the persons in this field all hope to synthesize various compounds with different structures, and explore the new targets to overcome above shortcomings.
Content of invention In order to solve above problems, the present invention provides pyrazolo[3,4-d]pyrimidine derivatives with novel structures.
The compounds of formula (I), or the pharmaceutically acceptable salts thereof, or the solvates thereof:
                In which,        R1 represents —NH2, —NH(C1-C4 alkyl) or —N(C1-C4 alkyl)2;        R2 represents hydrogen or C1-C6 alkyl;        R3 represents hydrogen or C1-C6 alkyl;        OR4 represents the substituent in any position of the benzene ring, R4 represents —(R5O)n—R6—X;        n represents the positive integer of 1˜10;        R5 and R6 are independently selected from the group of methylene, ethylidene, propylidene, butylidene, pentylidene, hexylidene, heptylidene, octylidene, nonylidene, or decylidene, respectively;        X represents halogen, —OH, or —OSO2—R7, R7 represents phenyl or phenyl substituted with one or more C1-C6 alkyls;        
Further, R1 is —NH2.
Further, R2 is hydrogen.
Further, R3 is C1-C6 alkyl, preferably n-butyl or tert-butyl.
Further, R1 is —NH2, and R2 is hydrogen, and R3 represents C1-C6 alkyl, preferably n-butyl or tert-butyl.
Further, n is 3, 4, or 5.
Further, R5 and R6 are both ethylidenes.
Further, X is p-methylbenzenesulfonyl group.
Further, said compounds are one of the followings:
                Ts represents p-methylbenzenesulfonyl group.        
The present invention also provides the uses of above compounds, or solvates thereof, or pharmaceutically acceptable salts thereof in the preparation of anti-tumor drugs.
Further, said drugs are those for the treatment of lung cancer.
Further, said lung cancer is non-small-cell lung carcinoma.
The present invention also provides a pharmaceutical composition, that is a formulation prepared by using above compounds, or solvates thereof, or pharmaceutically acceptable salts thereof as active constituents, with the addition of pharmaceutically acceptable excipients.
In the present invention, said C1-C4 alkyl means C1, C2, C3, and C4 alkyl, i.e. straight or branch chain alkyl having 1˜4 carbons, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl and so on. Similarly, said C1-C6 alkyl means C1, C2, C3, C4, C5, and C6 alkyl, i.e. straight or branch chain alkyl having 1˜6 carbons, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, and so on.
In the present invention, “treatment” further includes a relapse prevention or a phase prevention, as well as treating acute or chronic signs, symptoms and/or malfunctions. The treatment may be a symptomatic treatment, such as inhibiting symptoms. It can be realized in a short term, regulated in a medium term, or can be mentioned as long term therapy, such as for a maintenance therapy.
Said “prevention” includes delaying and/or preventing the attack of disorders, diseases, or conditions and/or concomitant symptoms thereof; preventing the infection of disorders, diseases, or conditions to the objects; or the methods reducing the risk of objects having disorders, diseases, or conditions. In the present invention, “pharmaceutically acceptable” means a carrier, a vector, a diluent, a adjuvant and/or a resultant salt that can be chemically or physically compatible with other constituents forming certain pharmaceutical dosage form, and physiologically compatible with acceptors.
In the present invention, “salt” means an acid salt and/or basic salt that is formed by a compound or its stereoisomer and inorganic and/or organic acid and base, and also includes amphoteric ion salts (inner salts), and further includes quaternary ammonium salts, such as alkyl ammonium salts. These salts can be directly obtained during the final separation and purification of compounds. These salts can also be obtained by suitably mixing a compound or its steroisomer with a certain amount of acid or base (such as an equivalent amount). These salts may form precipitation in the solution and can be collected by filtration method, or recovered after evaporation of solvent, or prepared by freeze drying after reaction in aqueous medium. In the present invention, said salts can be hydrochlorate, sulfate, citrate, benzenesulphonate, hydrobromate, hydrofluoride, phosphate, acetate, propionate, succinate, oxalate, malate, succinate, fumarate, maleate, tartrate or trifluoroacetate.
Experimental results show that compounds of the present invention have significant inhibitory action on lung cancer cell lines A549 and H1299, with a wide market outlook.
Obviously, based on above content of the present invention, according to the common technical knowledge and the conventional means in the field, without department from above basic technical spirits of the present invention, other various modifications, alternations or changes can further be made.
By following specific examples of said embodiments, above content of the present invention is further illustrated. But it should not be construed that the scope of above subject of the present invention is limited to following examples. The techniques realized based on above content of the present invention are all within the scope of the present invention.